EP 3765097 A1 20210120 - 2-ALKOXY-6-[18F]FLUORONICOTINOYL SUBSTITUTED LYS-C(O)-GLU DERIVATIVES AS EFFICIENT PROBES FOR IMAGING OF PSMA EXPRESSING TISSUES
Title (en)
2-ALKOXY-6-[18F]FLUORONICOTINOYL SUBSTITUTED LYS-C(O)-GLU DERIVATIVES AS EFFICIENT PROBES FOR IMAGING OF PSMA EXPRESSING TISSUES
Title (de)
2-ALKOXY-6-[18F]FLUORNICOTINOYL-SUBSTITUIERTE LYS-C(O)-GLU-DERIVATE ALS EFFIZIENTE SONDEN ZUR BILDGEBUNG VON PSMA-EXPRIMIERENDEN GEWEBEN
Title (fr)
DÉRIVÉS DE LYS-C(O)-GLU SUBSTITUÉS PAR LE 2-ALCOXY-6-[18F]FLUORONICOTINOYLE EN TANT QUE SONDES EFFICACES POUR LA VISUALISATION PAR IMAGERIE DE TISSUS EXPRIMANT LE PSMA
Publication
Application
Priority
- EP 18162380 A 20180316
- EP 2019056578 W 20190315
Abstract (en)
[origin: WO2019175405A1] 6-[18HF]Fluoro-2-alkoxynicotinoyl substituted Lys-C(O)-Glu derivatives were identified as efficient imaging probes for PSMA expressing tissues in comparison to other known PSMA specific ligands like [18F]DCFPyL, [68Ga]HBED-CC-PSMA, [18F]PSMA-1007 and [A118F]HBED-CC-PSMA. Unexpectedly, the 6-[18F]fluoro-2-alkoxy and 6-[18F]fluoro-4- alkoxy substituted analogs showed significant differences in accumulation in PSMA expressing prostate tumor cells. Whereas the 2-alkoxy derivative showed cellular uptake values higher than [18F]DCFPyL, the cellular uptake of the corresponding 4-alkoxy substituted derivative was significantly lower. Furthermore, in vivo PET studies with 2- alkoxy-substituted probes demonstrated excellent visualization of PSMA positive ganglia with extremely high target to background ratio. In contrast, the 4-alkoxy substituted derivatives showed less favorable biodistribution with significantly lower uptake in PSMA positive tissues. Especially, the 18F-labeled 2-methoxy derivate ((2S)-2-({[(1 S)- 1 -carboxy-5- [(6-[18F] fluoro-2-methoxypyridin-3-yl)formamido]pentyl ]carbamoyl} -amino)pentanedioic acid) demonstrated exceptional clinical efficiency in detecting small PCa lesions, including those which could not be visualized with [68Ga]HBED-CC-PSMA representing currently the gold standard for the diagnosis of recurrent PCa. Furthermore, this probe is easily accessible on a preparative scale in commercially available automated synthesis modules like GE FASTlab and TRACERlab FX N Pro. Consequently, the novel probe is a valuable tool for the visualization of ganglia and reendothelialization as well as for the diagnosis of glioma, neuropathic pain and atherosclerotic plaques.
IPC 8 full level
A61K 51/04 (2006.01); C07B 59/00 (2006.01)
CPC (source: EP US)
A61K 51/0455 (2013.01 - EP US); C07B 59/002 (2013.01 - EP US); C07D 213/82 (2013.01 - US)
Citation (search report)
See references of WO 2019175405A1
Designated contracting state (EPC)
AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
Designated extension state (EPC)
BA ME
DOCDB simple family (publication)
WO 2019175405 A1 20190919; DK 3765097 T3 20220523; EP 3765097 A1 20210120; EP 3765097 B1 20220427; ES 2914986 T3 20220620; HR P20220671 T1 20220902; HU E059482 T2 20221128; PL 3765097 T3 20220822; PT 3765097 T 20220601; US 11542234 B2 20230103; US 2021032206 A1 20210204
DOCDB simple family (application)
EP 2019056578 W 20190315; DK 19710421 T 20190315; EP 19710421 A 20190315; ES 19710421 T 20190315; HR P20220671 T 20190315; HU E19710421 A 20190315; PL 19710421 T 20190315; PT 19710421 T 20190315; US 201916981456 A 20190315